The current study represents a single institution retrospective observational case series which was performed at the Artemed Clinic Munich South, Germany between 2019 and 2022. Consecutive patients on ticagrelor and/or rivaroxaban with an urgent CABG indication and eligibility for OPCAB surgery due to comorbidity were included.

The study was conducted in accordance with the Declaration of Helsinki and the protocol was approved by the Ethics Committee of the University of Munich, Germany (approval number: 21–0198). Patient consent was waived due to the retrospective character of the study and de-identified dataset. In the present analysis, an individualized approach was undertaken to ensure a favorable benefit: risk profile in each patient before proceeding with this intervention during OPCAB surgery and was discussed with all patients during the informed consent process for surgery or was considered as best practice decision during the surgery in the instance of excessive bleeding.

Inclusion criteria included: (a) urgent cardiac surgery in patients aged 18 years or over, male or female (women of child-bearing potential with a negative pregnancy test at screening) on ticagrelor and/or rivaroxaban and (b) use of the hemoadsorption cartridge (Cytosorb®, CytoSorbents, Princeton, NJ, USA) for AT removal during OPCAB surgery.

Exclusion criteria included concomitant surgery (e.g. aortic valve surgery etc.), patients on chemotherapy, immunosuppressive medication, other antithrombotic drugs than ticagrelor or rivaroxaban or steroids.

Before surgery, citrate anticoagulation was used when the adsorber was integrated into a dialysis pump to start the hemoadsorption therapy. In cases where the adsorber was inserted in the apharesis pump PUR-01, 5,000IE of heparin were administered to initialize the start of the hemoadsorption therapy. After skin-incision, following sternotomy and left internal thoracic artery (LITA) harvesting, another 15,000IE of heparin were administered (targeted activated clotting time > 300s). After completion of all anastomoses, protamine was given.

The CytoSorb® adsorber consists of a 300 mL cartridge which contains biocompatible porous polymer beads. These beads bind hydrophobic substances with a molecular size of up to 60 kDa from whole blood by pore capture and its irreversible surface adsorption properties. Intraoperative antithrombotic removal via hemoadsorption allows for on-pump ticagrelor and rivaroxaban removal according to the instructions for use and bears CE-mark approval for this indication. Adsorption is also concentration-dependent and the adsorber is approved to remove cytokines, bilirubin, myoglobin, rivaroxaban and ticagrelor. On the other hand, albumin or coagulation factors are not removed, however, certain drugs, e.g. vancomycin are removed [8]. A detailed list of adsorbed substances is given in Scheier et al. and for specific drugs, therapeutic drug monitoring is recommended [9]. The overall adsorption surface area in one adsorption cartridge is more than 45,000m2. The adsorber has been demonstrated to remove antithrombotic medications such as ticagrelor [10] and rivaroxaban [7, 11] and is CE-mark approved to remove these AT’s during CPB. In this present analysis, the adsorber was incorporated into a separate apheresis or dialysis pump during off-pump surgery.

The set-up has been described elsewhere by our group, but in brief: The CytoSorb adsorber was integrated with standard dialysis connectors into an extracorporeal circuit in hemoperfusion mode (multiFiltrate, Fresenius Medical Care, Bad Homburg, Germany) using citrate anticoagulation and was run using standard settings (tubes and hemofilter, Kit Ci-Ca CVVHD 1000, Fresenius Medical Care; dialysate, Ci-Ca Dialysate K2, 2 L/h, Fresenius Medical Care). No ultrafiltration was used. Tubes were connected to a large 12-F, 3-lumen catheter (Arrow International Inc., Reading, PA, USA) and were implanted into the femoral vein of the patient. The blood flow rate of this system was set up to 150 mL/h [12].

Detailed instructions for use of the PUR-01 pump are described in the “Apheresis Equipment Pure Adjust PUR-01 Operating Instructions” (Manual No. 1055en-R8, 2020-9, Nikkisio CO., Ltd., Tokyo, Japan). In brief: A stand-alone apheresis pump, Pure Adjust PUR-01 (Nikkisio Co., Ltd., Tokyo, Japan) was used (Fig. 1). The apheresis machine has the function of a direct hemoperfusion pump. The machine was equipped with a venous blood tubing line set (ABT-023P Series, Nikkisio Co., Ltd., Tokyo, Japan). The lines of the device were connected to a 12 F and 3-lumen high-flow catheter (Arrow International Inc., Reading, PA, USA) inserted into the cervical or femoral vein of the patient. With the start of PUR-01, a 5000 I.E. single injection of heparin was given. During hemoadsorption the blood flow rate was set up to 200mL/min.

Hemoadsorption device (CytoSorb® 300, CytoSorbents Inc., Princeton, NJ, USA) incorporated in the apheresis machine PUR-01 (Nikkisio Co., Ltd., Tokyo, Japan)

Ticagrelor or rivaroxaban was stopped before surgery. The first four patients had the high-flow catheter implanted under local anesthesia prior to surgery, on the ICU. Hemoadsorption was initiated approximately one hour before the patient was transferred to the operation room and was continued for approximately 1 to 1.5 h during the operation for a total treatment time of 145 ± 33 min, to eliminate the AT. The following 6 patients received a 12 F, 3-lumen high-flow catheter implanted into the right femoral or cervical vein after initiation of standard anesthetic care. Adsorption was initiated parallel to skin incision.

Following sternotomy, the internal thoracic artery and simultaneously the saphenous vein harvesting was performed. Prior to the bypass anastomosis, another 15,000 units of heparin were administered (200 IE Heparin/KG body weight with activated coagulation time > 300 s). Myocardial revascularization was performed using an Octopus® tissue stabilizer (Medtronic, Minneapolis, MN, USA) starting with the LITA to the left anterior descending artery in all patients. In one patient, the right internal thoracic artery was grafted to the circumflex artery. For all other bypass grafts, the saphenous vein was used. After the completion of all bypass anastomoses, protamine was given and hemoadsorption was discontinued. Transit-time flow measurement was performed thereafter. The procedure was finished using standard techniques. Patients were then transferred to the intensive care unit (ICU).

Primary outcome was the incidence of bleeding complications according to the Bleeding Academic Research Consortium (BARC) [13]. Secondary outcomes included 24-h chest tube drainage (CTD), blood product transfusions, re-operation for bleeding and in-hospital mortality.